This project is concerned with the pathogenesis of the immunologically mediated inflammatory response at the site of persistent local antigenic stimulation. To study this problem we have developed "peroxidase arthritis", in which an immunologically mediated inflammatory response is evoked by repeated injection of horseradish peroxidase into the rabbit knee joint. The synovitis, which resembles rheumatoid arthritis histologically, is notable in that both antigen and specific antibody can be localized precisely by ultrastructural cytochemical techniques. Although local antibody synthesis can be demonstrated in immunoblasts and plasma cells within the synovial tissue, the site of initial sensitization and the nature of subsequent traffic of sensitized lymphocytes is uncertain. Our data suggest that at least some of the lymphocytes are initially sensitized in the regional lymph node and reach the synovial tissue via the bloodstream. Whether other lymphocytes are initially sensitized in the synovial tissue is as yet unknown. Also, whether sensitized lymphocytes accumulate in the joint because of the presence of specific antigen, or whether their accumulation is a nonspecific consequence of the presence of inflammation is unclear. Experiments planned for the coming year are designed to explore these questions.